The DNA tumor virus SV40 is capable of inducing tumors in test animals and transforming cells in culture. One of the oncogenes encoded by SV40, large T antigen, has been shown to be sufficient and necessary for the transforming ability of the virus. The mechanism by which this single viral protein can cause such enormous changes in cellular behavior remains a fundamental question of tumorigenicity. The goal of this research proposal is directed towards understanding the molecular events which initiate T antigen-mediated transformation. It has been suggested that by binding to the two cellular antioncogenes Rb and p53, T antigen can suppress their normal function. Some recent evidence indicates that SV40 T antigen may also carry an additional activity for transformation. The PSC protein sequence analysis methods would greatly help to identify this new activity and to characterize its role in cell proliferation. In addition, by comparing sequences of various T antigen domains to other proteins with similar functions, it should be possible to more rationally choose key T antigen sequences for mutagenic studies and to gain insight about the mechanisms used to bind to the tumor suppresor proteins Rb and p53. Thus analyzing the sequences of T antigen and proteins bound by it will contribute towards delineating the mechanisms of its function.